Characterization of chromanol 293B-induced block of the delayed-rectifier K+ current in heart-derived H9c2 cells

Life Sci. 2005 Apr 1;76(20):2275-86. doi: 10.1016/j.lfs.2004.09.036. Epub 2005 Jan 27.

Abstract

The effects of chromanol 293B on ion currents in rat embryonic heart-derived H9c2 cells were investigated in this study. Chromanol 293B suppressed the amplitude of delayed rectified K+ current (I(K)) in a concentration-dependent manner. The IC50 value for chromanol 293B-induced inhibition of I(K) was 8 microM. The I(K) present in these cells, the electrical properties of which resembled those for the Kv2.1-related K+ current, was sensitive to inhibition by quinidine or dendrotoxin, yet not by pandinotoxin-Kalpha, E-4031 or apamin. Chromanol 293B reduced the activation time constant of I(K) and the effective gating charge of this channel. However, little or no modification in the steady-state inactivation of I(K) in response to long-lasting conditioning pulses could be demonstrated in the presence of chromanol 293B. These results clearly demonstrate that chromanol 293B can effectively interact with the K+ channel functionally expressed in H9c2 myoblasts. The chromanol 293B-induced inhibition of these channels could primarily be attributed to open channel block.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chromans / pharmacology*
  • Dose-Response Relationship, Drug
  • Heart Ventricles / cytology
  • Ion Channel Gating / drug effects
  • Membrane Potentials / drug effects
  • Potassium / metabolism*
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels, Voltage-Gated / antagonists & inhibitors*
  • Rats
  • Sulfonamides / pharmacology*
  • Ventricular Function*

Substances

  • Chromans
  • Potassium Channel Blockers
  • Potassium Channels, Voltage-Gated
  • Sulfonamides
  • 6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane
  • Potassium